ABSTRACT Purpose This study aims to determine the proportion of bone marrow dysplasia in advance of HIV infection. Patients and methods A cross-sectional study was conducted on advanced HIV patients, stage III and IV, with cytopenia at Hasan Sadikin General Hospital, Bandung, from January 2021 to November 2023. Patient characteristics and laboratory data were obtained from patients diagnosed with HIV stages III and IV who presented with cytopenia and underwent bone marrow examinations, as documented in the medical records. The differences between the two groups were analyzed using the Mann–Whitney U test or the Independent T-test for numerical data and Chi-square or Fisher’s exact for categorical data. Results A total of 42 subjects were enrolled, consisting of 8 (19%) HIV stage III and 34 (81%) stage IV patients. Patients with HIV stage IV exhibited a higher incidence of pancytopenia, with 15 cases (44.1%). The bone marrow cellularity in HIV stage IV was predominantly hypocellular, accounting for 22 cases (64.7%). Dyserythropoiesis was the most common type of bone marrow dysplasia observed in HIV stage IV, present in 19 cases (55.9%). The prevalence of Bone Marrow Dysplasia in HIV stage IV was higher than in HIV stage III, with 23 (64.7%) and 2 (37.5%), respectively (p = 0.2348) Conclusion Cytopenias related to HIV are common and tend to worsen as the disease advances. This emphasizes the importance of investigating the potential for bone marrow dysplasia and conducting cytogenetic diagnostic testing for myelodysplastic syndromes (MDS), as a significant non-AIDS-defining hematological malignancy in individuals with advanced HIV.

ABSTRACT Background Congenital thrombocytopenia represents a diagnostically challenging group of disorders due to overlapping clinical presentations among various etiologies. Case Presentation A 3-month-old infant presented with severe thrombocytopenia (platelet count 6,000/μL), neutropenia, and bone marrow findings of megakaryocytic hypoplasia, initially suggestive of congenital amegakaryocytic thrombocytopenia (CAMT). Comprehensive genetic testing identified a homozygous pathogenic variant in the GNE gene (NM_001128227.2:c.1768G > A, p.Gly590Arg), establishing the definitive diagnosis of GNE-related thrombocytopenia (Thrombocytopenia-12, THC12). Clinical significance This case highlights three critical aspects: first, the essential role of genetic testing in differentiating congenital thrombocytopenias; second, the distinct management implications of THC12 compared to CAMT; and third, the need for long-term monitoring given the potential for late-onset myopathy despite initial isolated hematologic manifestations. Management Therapeutic interventions included intravenous immunoglobulin, platelet transfusions, and thrombopoietin receptor agonists, with concurrent evaluation for potential hematopoietic stem cell transplantation. Conclusion This report underscores THC12 as an important diagnostic consideration in infants with congenital thrombocytopenia and emphasizes the necessity of genetic confirmation to guide appropriate clinical management and family counseling.

ABSTRACT Objectives: This study aimed to compare clinical, and molecular features between acute myeloid leukemia (AML) patients aged <50 and ≥50 years, while also assessing their respective treatment outcomes and prognostic factors. Methods: We conducted a retrospective analysis of clinical data from AML patients treated at our institution between October 2015 and June 2021, supplemented by data extracted from the SEER database spanning 2000 to 2019. Survival outcomes were evaluated using Kaplan-Meier methodology. Results: In patients aged ≥50 years, we observed higher prevalence of DNMT3A, IDH2, and TP53 mutations along with −5/del (5q) karyotype abnormalities. The treatment outcomes were suboptimal, with a complete response (CR) rate of 45.9%, relapse rate of 60.8%, and two-year overall survival (OS) rate of 33.3%. VEN-treated chemotherapy-intolerant patients showed significantly improved two-year OS (36.0% vs 12.1% in non-VEN group; P = 0.006). In contrast, patients aged <50 years exhibited a distinct molecular profile characterized by a predominance of NRAS, biallelic CEBPA, WT1, and C-KIT mutations, along with a higher incidence of RUNX1-RUNX1T1 and CBFB-MYH11 fusion genes. This group demonstrated more favorable clinical outcomes, with a CR rate of 73.1%, relapse rate of 36.8%, and two-year OS rate of 68.3%. Conclusions: This study revealed that patients aged ≥50 years displayed more complex genetic aberration profiles and experienced significantly poorer prognoses compared to their younger counterparts. These findings provided novel insights for optimizing treatment strategies for middle-aged and elderly AML patients in the Chinese population.

ABSTRACT Objectives: Numerous observational research avenues have identified a possible correlation between aplastic anemia and autoimmune diseases, rooted in analogous dysfunctional immune responses. Nevertheless, causal link between autoimmune diseases and aplastic anemia remains elusive. The study aims to investigate the causal association of autoimmune diseases and aplastic anemia. Methods: This study leveraged summary data from genome-wide association studies pertaining to six prevalent autoimmune diseases: ulcerative colitis, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, celiac disease, and type 1 diabetes mellitus, procured from expansive, public genome-wide association studies meta-analysis databases. Aplastic anemia – related genetic information was extracted from the UK Biobank. Utilizing single nucleotide polymorphisms as genetic instruments – meeting criteria P < 5 × 10−8 and linkage disequilibrium [LD] r² < 0.001 – the study employed Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis to gauge the sensitivity concerning the impact of autoimmune diseases on aplastic anemia. Results: The findings underscore a definitive causal relationship between systemic lupus erythematosus and aplastic anemia, as evidenced by the statistics (ORIVW = 1.193, 95% CI 1.013–1.404, P = 0.035). Duplicate SLE GWAS from the FinnGen database demonstrated that patients with SLE are more susceptible to AA (ORIVW = 1.193, 95% CI 1.013–1.404, P = 0.035). Additionally, the Mendelian randomization analysis reported no evidence of horizontal or directional pleiotropy. Conclusions: In summary, the study suggests that systemic lupus erythematosus could serve as a potential risk factor contributing to the onset of aplastic anemia. To substantiate this hypothesis, ensuing studies encompassing larger sample sizes are warranted.

Objectives The aim of this study was to characterize the clinical features and outcomes of patients with JAK2 V617F- and CALR-unmutated essential thrombocythemia (ET) and to identify potential driver mutations through whole-exome sequencing (WES). Methods This was a cross-sectional study including patients diagnosed with ET between 2007 and 2024. Clinical characteristics and outcomes were compared between patients with and without JAK2V617F and CALR mutations. WES was analyzed in JAK2V617F- and CALR-unmutated ET patients. Results Thirty-nine out of 162 ET patients (24%) were JAK2V617F- and CALR-unmutated. This group was younger than patients in the JAK2V617F mutated group (mean age 53.7 vs. 61.1 years, p = 0.012) and had lower incidence of thrombotic events (5.1% vs. 9.1%, p = 0.327). The median overall survival was 13.51 years compared to 12.61 years in patients with JAK2V617F or CALR mutations (p = 0.63). There were no statistically significant differences in clinical symptoms, incidence of thrombosis, bleeding, myelofibrosis, or leukemic transformation. WES was analyzed in 15 patients. Uncommon MPL mutations were identified, including MPLL265F, MPLP70L, and MPLR321Q. Potential novel CALR mutations were detected in exon 5 (c.540C > T, N180 = ) and exon 6 (c.703-3del). Non-driver gene mutations were detected, including RUNX1 (57.1%), ASXL1, DNMT3A, SETBP1, and MSH6. Discussion and Conclusions Patients with JAK2V617F- and CALR-unmutated ET tend to present at a younger age and exhibit a lower incidence of thrombosis compared to those with JAK2V617F-mutated ET. The application of WES enabled the detection of uncommon and potential driver mutations in JAK2V617F- and CALR-unmutated ET.

ABSTRACT Objective To identify simple clinical predictors of prognosis in multiple myeloma (MM) after chemotherapy and assess their predictive value. Methods We retrospectively analyzed 164 newly diagnosed MM patients treated with proteasome inhibitor– and/or immunomodulatory drug–based chemotherapy between 2018 and 2024. Baseline data included demographics, DS/ISS stage, haemoglobin (Hb), platelets, albumin, creatinine, calcium, lactate dehydrogenase (LDH), erythrocyte sedimentation rate, and serum β2-microglobulin (β2-MG). Treatment responses after four cycles (CR/VGPR vs ≤PR) and survival outcomes were recorded. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Cox models identified independent prognostic factors. Landmark 2-year ROC curves evaluated discriminative ability. Results After four cycles, 95/164 patients (57.9%) achieved CR/VGPR and 69 (42.1%) ≤PR. During a median follow-up of 31 months, 85 deaths and 112 progression events occurred. Multivariable analysis showed that age >60 years, Hb ≤85 g/L, β2-MG>3.5 mg/L, and ≤PR were independently associated with shorter OS, whereas Hb ≤85 g/L and ≤PR predicted shorter PFS. Two-year AUCs for mortality prediction were 0.601 for age, 0.624 for Hb, 0.647 for β2-MG, and 0.731 for response; for PFS prediction, AUCs were 0.668 for Hb and 0.749 for response, indicating fair but limited standalone discrimination. Conclusion Advanced age, severe anaemia, elevated β2-MG, and suboptimal early response are simple, readily available predictors of adverse survival in MM. Although their individual discriminative power is modest, these factors may inform pragmatic risk stratification, especially where cytogenetic and MRD testing are unavailable, and could be incorporated into future composite prognostic scores.

ABSTRACT Background: Thrombotic diseases are a global challenge. Warfarin remains the anticoagulant of choice in low- and middle-income countries. In 2017, a study reported suboptimal anticoagulation control of 29.4%, compared to the target of ≥ 65%, in patients who attended the Windhoek Central Hospital’s warfarin clinic. Objective: Factors contributing to the suboptimal anticoagulation control had to be explored. Methods: To achieve this, 72 patients from the interventional cohort at the clinic were interviewed. Results: The majority (39%) of respondents had dosage-related factors, followed by 21% with diet-related factors, 19% reported factors associated with social determinants of health, and the least (5.6%) due to drug interactions in patients with a co-diagnosis of tuberculosis. Conclusion: The study highlighted the need for improved healthcare system support, such as equipping non-physician health cadres (pharmacists and nurses) with the ability to prescribe warfarin therapy and roll out point-of-care testing for patients with limited access to primary healthcare settings, improving access to medication at the primary healthcare facilities, and patient education to improve warfarin therapy outcomes.

ABSTRACT Introduction Blood is vital for life, but ensuring a safe and sufficient supply remains a public health challenge, particularly in low-resource settings. This study explores the knowledge, attitudes, practices, and factors influencing blood donation among pre-service teacher trainees at Finote Selam College of Education, Northwest Ethiopia. Methods A cross-sectional survey was conducted using proportionate sampling. Data were collected through questionnaires completed by the participants themselves and analyzed using SPSS version 27, with results presented in descriptive narratives and tables. Results Of 277 participants, 27.8% were male and 72.2% female. While 55.6% demonstrated adequate knowledge of blood donation and 42.2% had a positive attitude, only 28.2% had ever donated blood. Key factors influencing donation practices included knowledge, attitude, academic department, and religious affiliation. Conclusion Although participants had reasonable knowledge of blood donation, positive attitudes and actual donation rates were low. Department-specific awareness programs and regular donation drives, in partnership with health institutions, could enhance donation rates and foster social responsibility among future educators.

ABSTRACT Objectives To elucidate the mechanisms by which leukemia-derived exosomes induce immunosuppression in dendritic cells (DCs) and identify potential therapeutic targets. Methods The optimal exosome dosage (20 µg/ml) for DC treatment was determined via gradient concentration experiments. Transcriptomics and qPCR validation explored molecular pathways. DC phenotype was assessed for maturation markers (CD83/CD86), antigen presentation (CD1a), and immune receptors (TLR2). Cytokine levels (IL-6, IL-17, TNF-α, IL-4) were quantified. Multi-omics analysis identified key signaling pathways. Clinical validation utilized samples from AML patients. Results Exosome treatment induced broad DC immunosuppression, characterized by significant downregulation of pro-inflammatory cytokines (IL-6, IL-17, TNF-α) and upregulation of anti-inflammatory IL-4. Phenotypic analysis revealed selective inhibition of CD1a and TLR2, while maturation markers (CD83/CD86) remained unaltered. Multi-omics identified TNF-β signaling as the primary immunosuppressive pathway. qPCR confirmed elevated TGF-β2 and mitochondrial ribosomal protein MRPL58, alongside reduced TLR2. Clinical studies in AML patients validated upregulation of TGF-β2, MRPL58, and exosomal markers. Exosomes impaired DC antigen presentation, immune response, and metabolic activity. Discussion MRPL58 is a novel mediator of exosome-driven immunosuppression, implicating metabolic reprograming. Selective CD1a/TLR2 inhibition suggests exosomes evade immune detection while permitting DC maturation, a strategy favoring leukemia immune escape. Targeting exosome-DC interactions (e.g. blocking exosomal signals or MRPL58) may restore anti-tumor immunity. Conclusion Leukemia exosomes suppress DC function primarily through MRPL58-associated metabolic modulation and TNF-β signaling. MRPL58 represents a promising therapeutic target. Disrupting exosome-mediated immunosuppression could enhance DC-based vaccines and combination immunotherapies for leukemia.

ABSTRACT Objectives: Prior research has highlighted immune cells’ critical role in multiple myeloma (MM) pathogenesis, yet the causal relationships between them have remained obscure. Methods: We utilized data from genome-wide association studies (GWAS) of European cohorts to conduct a Mendelian Randomization (MR) analysis, aiming to establish causal links between immune cell phenotypes and MM. We selected single nucleotide polymorphisms (SNPs) associated with immune cell traits at a suggestive significance threshold (P < 1 × 10−5) to ensure sufficient instrumental variables, with F-statistics (>10) calculated to assess instrument strength. Multiple MR methods were applied to 731 immune phenotypes and MM. Results: Eight immunophenotypes showed nominal associations with MM risk (P < 0.05). However, no associations survived the strict Bonferroni correction for multiple testing. Suggestive causal effects of MM on immunophenotypic traits are predominantly negative, implying that MM may impair the functionality of immune cells. Discussion: This study uses GWAS data to elucidate the genetic impact of immune cells on the initiation and progression of MM. It presents genetic evidence suggesting that immune cells could alter MM risk based on a thorough genetic analysis. Bidirectional two-sample MR identified eight distinct immunophenotypes (encompassing four immune signatures: MFI, RC, AC, MP) with causal effects on MM. Conclusion: Our study provides preliminary evidence for potential causal links between specific immune traits and MM risk. Independent replication in larger cohorts and functional validation are warranted given the nominal significance of these associations, which may inform future immunotherapeutic investigations. These findings contribute to a better understanding of the complex immune – MM interplay and may guide future investigations into immunotherapeutic approaches.